XGEVA

XGEVA is an FDA-registered drug product whose active ingredient is DENOSUMAB. It is labelled by Amgen, Inc taken by subcutaneous and marketed as a human prescription drug product. Identifiers on file: NDC 55513-730, application BLA125320, label effective 20260623. It is one of 4 FDA drug label records sharing the active ingredient DENOSUMAB. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing DENOSUMAB are most often described in connection with: multiple myeloma, solid tumors, giant cell, tumor bone, hypercalcemia malignancy, xgeva indicated, prevention skeletal-related, events patients. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE Xgeva is a RANK ligand (RANKL) inhibitor indicated for: Prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors. ( 1.1 ) Treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity. ( 1.2 , 14.3 ) Treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy. ( 1.3 ) 1.1 Multiple Myeloma and Bone Metastasis from Solid Tumors Xgeva is indicated for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors. 1.2 Giant Cell Tumor of Bone Xgeva is indicated for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity [see Clinical Trials ( 14.2 )] . 1.3 Hypercalcemia of Malignancy Xgeva is indicated for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.

2 DOSAGE AND ADMINISTRATION Xgeva should be administered by a healthcare provider. ( 2.1 ) Xgeva is intended for subcutaneous route only and should not be administered intravenously, intramuscularly, or intradermally. ( 2.1 ) Multiple Myeloma and Bone Metastasis from Solid Tumors: Administer 120 mg every 4 weeks as a subcutaneous injection in the upper arm, upper thigh, or abdomen. ( 2.2 ) Giant Cell Tumor of Bone: Administer 120 mg every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy. Administer subcutaneously in the upper arm, upper thigh, or abdomen. ( 2.3 ) Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia. ( 2.2 , 2.3 ) Hypercalcemia of Malignancy: Administer 120 mg every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy. Administer subcutaneously in the upper arm, upper thigh, or abdomen. ( 2.4 ) 2.1 Important Administration Instructions Xgeva should be administered by a healthcare provider. Xgeva is intended for subcutaneous route only and should not be administered intravenously, intramuscularly, or intradermally. 2.2 Multiple Myeloma and Bone Metastasis from Solid Tumors The recommended dose of Xgeva is 120 mg administered as a subcutaneous injection every 4 weeks in the upper arm, upper thigh, or abdomen. Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia [see Warnings and Precautions ( 5.3 )]. 2.3 Giant Cell Tumor of Bone The recommended dose of Xgeva is 120 mg administered every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy. Administer subcutaneously in the upper arm, upper thigh, or abdomen. Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia [see Warnings and Precautions ( 5.3 )]. 2.4 Hypercalcemia of Malignancy The recommended dose of Xgeva is 120 mg administered every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy. Administer subcutaneously in the upper arm, upper thigh, or abdomen. 2.5 Preparation and Administration Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Xgeva is a clear, colorless to pale yellow solution that may contain trace amounts of translucent to white proteinaceous particles. Do not use if the solution is discolored or cloudy or if the solution contains many particles or foreign particulate matter. Prior to administration, Xgeva may be removed from the refrigerator and brought to room temperature up to 25°C (77°F) by standing in the original container. This generally takes 15 to 30 minutes. Do not warm Xgeva in any other way [see How Supplied/Storage and Handling ( 16 )]. Use a 27-gauge needle to withdraw and inject the entire contents of the vial. Do not re-enter the vial. Discard vial after single entry.

4 CONTRAINDICATIONS Hypocalcemia ( 4.1 ) Known clinically significant hypersensitivity to Xgeva or denosumab products ( 4.2 ) 4.1 Hypocalcemia Pre-existing hypocalcemia must be corrected prior to initiating therapy with Xgeva [s ee Warnings and Precautions ( 5.3 )] . 4.2 Hypersensitivity Xgeva is contraindicated in patients with known clinically significant hypersensitivity to Xgeva or denosumab products [see Warnings and Precautions ( 5.2 ) and Adverse Reactions ( 6.2 )] .

6 ADVERSE REACTIONS The following adverse reactions are discussed below and elsewhere in the labeling: • Hypersensitivity [see Warnings and Precautions ( 5.2 )] • Hypocalcemia [see Warnings and Precautions ( 5.3 ) and Use in Specific Populations ( 8.6 ) ] • Osteonecrosis of the Jaw [see Warnings and Precautions ( 5.4 )] • Atypical Subtrochanteric and Diaphyseal Femoral Fracture [see Warnings and Precautions ( 5.5 )] • Hypercalcemia following treatment discontinuation in patients with giant cell tumor of bone and in patients with growing skeletons [see Warnings and Precautions ( 5.6 ) and Use in Specific Populations ( 8.4 ) ] • Multiple vertebral fractures (MVF) following treatment discontinuation [see Warnings and Precautions ( 5.7 )] Bone Metastasis from Solid Tumors: Most common adverse reactions (≥ 25%) were fatigue/asthenia, hypophosphatemia, and nausea. ( 6.1 ) Multiple Myeloma: Most common adverse reactions (≥ 10%) were diarrhea, nausea, anemia, back pain, thrombocytopenia, peripheral edema, hypocalcemia, upper respiratory tract infection, rash, and headache. ( 6.1 ) Giant Cell Tumor of Bone: Most common adverse reactions (≥ 10%) were arthralgia, headache, nausea, back pain, fatigue, and pain in extremity. ( 6.1 ) Hypercalcemia of Malignancy: Most common adverse reactions (> 20%) were nausea, dyspnea, decreased appetite, headache, peripheral edema, vomiting, anemia, constipation, and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Inc. at 1-800-77-AMGEN (1-800-772-6436) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Bone Metastasis from Solid Tumors The safety of Xgeva was evaluated in three randomized, double-blind, double-dummy trials [see Clinical Trials ( 14.1 )] in which a total of 2841 patients with bone metastasis from prostate cancer, breast cancer, or other solid tumors, or lytic bony lesions from multiple myeloma received at least one dose of Xgeva. In Studies 20050136, 20050244, and 20050103, patients were randomized to receive either 120 mg of Xgeva every 4 weeks as a subcutaneous injection or 4 mg (dose adjusted for reduced renal function) of zoledronic acid every 4 weeks by intravenous (IV) infusion. Entry criteria included serum calcium (corrected) from 8 to 11.5 mg/dL (2 to 2.9 mmol/L) and creatinine clearance 30 mL/min or greater. Patients who had received IV bisphosphonates were excluded, as were patients with prior history of ONJ or osteomyelitis of the jaw, an active dental or jaw condition requiring oral surgery, non-healed dental/oral surgery, or any planned invasive dental procedure. During the study, serum chemistries including calcium and phosphorus were monitored every 4 weeks. Calcium and vitamin D supplementation was recommended but not required. The median duration of exposure to Xgeva was 12 months (range: 0.1-41) and median duration on-study was 13 months (range: 0.1-41). Of patients who received Xgeva, 46% were female. Eighty-five percent were White, 5% Hispanic/Latino, 6% Asian, and 3% Black. The median age was 63 years (range: 18-93). Seventy-five percent of patients who received Xgeva received concomitant chemotherapy. The most common adverse reactions in patients (incidence greater than or equal to 25%) were fatigue/asthenia, hypophosphatemia, and nausea (see Table 1). The most common serious adverse reaction was dyspnea. The most common adverse reactions resulting in discontinuation of Xgeva were osteonecrosis and hypocalcemia. Table 1. Selected Adverse reactions reported in at least 10% of patients receiving Xgeva in Studies 20050136, 20050244, and 20050103, and meeting one of the following criteria: At least 1% greater incidence in Xgeva-treated patients, or Between-group difference (either direction) of less than 1% and more than 5% greater incidence in patients treated with zoledronic acid compared to placebo (US Prescribing Information for zoledronic acid) Adverse Reactions of Any Severity (Studies 20050136, 20050244, and 20050103) Body System Xgeva n = 2841 % Zoledronic Acid n = 2836 % GASTROINTESTINAL Nausea 31 32 Diarrhea 20 19 GENERAL Fatigue/Asthenia 45 46 INVESTIGATIONS Hypocalcemia Laboratory-derived and below the central laboratory lower limit of normal [8.3 - 8.5 mg/dL (2.075 - 2.125 mmol/L) for calcium and 2.2 - 2.8 mg/dL (0.71 - 0.9 mmol/L) for phosphorus] 18 9 Hypophosphatemia 32 20 NEUROLOGICAL Headache 13 14 RESPIRATORY Dyspnea 21 18 Cough 15 15 Severe Mineral/Electrolyte Abnormalities Severe hypocalcemia (corrected serum calcium less than 7 mg/dL or less than 1.75 mmol/L) occurred in 3.1% of patients treated with Xgeva and 1.3% of patients treated with zoledronic acid. Of patients who experienced severe hypocalcemia, 33% experienced 2 or more episodes of severe hypocalcemia and 16% experienced 3 or more episodes [see Warnings and Precautions ( 5.3 ) and Use in Specific Populations ( 8.6 )]. Severe hypophosphatemia (serum phosphorus less than 2 mg/dL or less than 0.6 mmol/L) occurred in 15% of patients treated with Xgeva and 7% of patients treated with zoledronic acid. Osteonecrosis of the Jaw (ONJ) In the primary treatment phases of Studies 20050136, 20050244, and 20050103, ONJ was confirmed in 1.8% of patients in the Xgeva group (median exposure of 12.0 months; range: 0.1-41) and 1.3% of patients in the zoledronic acid group. The trials in patients with breast (Study 20050136) or prostate (Study 20050103) cancer included an Xgeva open-label extension treatment phase where patients were offered Xgeva 120 mg once every 4 weeks (median overall exposure of 14.9 months; range: 0.1-67.2). The patient-year adjusted incidence (number of events per 100 patient years) of confirmed ONJ was 1.1% during the first year of treatment, 3.7% in the second year, and 4.6% per year thereafter. The median time to ONJ was 20.6 months (range: 4-53) [see Warnings and Precautions ( 5.4 )] . In a placebo-controlled clinical trial with an extension treatment phase evaluating Xgeva for the prevention of bone metastases in patients with non-metastatic prostate cancer (a patient population for which Xgeva is not indicated), with longer treatment exposure of up to 7 years, the patient-year adjusted incidence (number of events per 100 patient years) of confirmed ONJ was 1.1% during the first year of treatment, 3% in the second year, and 7% per year thereafter. Atypical Subtrochanteric and Diaphyseal Fracture In the clinical trial program, atypical femoral fracture has been reported in patients treated with Xgeva and the risk increased with longer duration of treatment. Events have occurred during treatment and after treatment was discontinued [see Warnings and Precautions ( 5.5 )] . Multiple Myeloma The safety of Xgeva was evaluated in an international, randomized (1:1), double-blind, active-controlled trial of patients with newly diagnosed multiple myeloma with treatment through disease progression [see Clinical Trials ( 14.2 )] . In this trial, patients received 120 mg Xgeva every 4 weeks as a subcutaneous injection (n = 850) or 4 mg (dose adjusted for renal function) of zoledronic acid intravenously (IV) every 4 weeks by IV infusion (n = 852). Entry criteria included serum calcium (corrected) from 8 to 11.5 mg/dL (2 to 2.9 mmol/L) and creatinine clearance 30 mL/min or greater. Patients who had received IV bisphosphonates were excluded, as were patients with prior history of ONJ or osteomyelitis of the jaw, an active dental or jaw condition requiring oral surgery, non-healed dental/oral surgery, or any planned invasive dental procedure. During the study, serum chemistries including calcium and phosphorus were monitored every 4 weeks. Calcium and vitamin D supplementation was recommended but not required. The median duration of exposure to Xgeva was 16 months (range: 1-50) and median duration on-study was 17 months (range: 0-49). Of patients who received Xgeva, 46% were female, 83% percent were White, 13% Asian, 3% Black or African American, and 4% Hispanic/Latino. The median age of the patients randomized to Xgeva was 63 years (range: 29-91) and all patients who received Xgeva received concomitant anti-myeloma chemotherapy. The adverse reaction profile of Xgeva in patients with multiple myeloma, Study 20090482, was similar to that observed in Studies 20050136, 20050244, and 20050103. The most common adverse reactions (incidence ≥ 10%) were diarrhea (34%), nausea (32%), anemia (22%), back pain (21%), thrombocytopenia (19%), peripheral edema (17%), hypocalcemia (16%), upper respiratory tract infection (15%), rash (14%), and headache (11%). The most common serious adverse reaction (incidence ≥ 5%) was pneumonia (8%). The most common adverse reaction resulting in discontinuation of Xgeva (≥ 1%) was osteonecrosis of the jaw. Hypocalcemia and Hypophosphatemia Severe hypocalcemia (corrected serum calcium less than 7 mg/dL or less than 1.75 mmol/L) and severe hypophosphatemia (serum phosphorus less than 2 mg/dL or less than 0.6 mmol/L) occurred in 2% and 21% patients treated with Xgeva, respectively. Osteonecrosis of the Jaw (ONJ) In the primary treatment phase of Study 20090482, ONJ was confirmed in 4.1% of patients in the Xgeva group (median exposure of 16 months; range: 1-50) and 2.8% of patients in the zoledronic acid group (median 15 months, range: 1-45 months). At the completion of the double-blind treatment phase of Study 20090482, the patient-year adjusted incidence (number of events per 100 patient years) of confirmed ONJ in the Xgeva group (median exposure of 19.4 months; range: 1-52) was 2% during the first year of treatment, 5% in the second year, and 4.5% per year thereafter. The median time to ONJ was 18.7 months (range: 1-44) [see Warnings and Precautions ( 5.4 )] . Giant Cell Tumor of Bone The safety of Xgeva was evaluated in two single-arm trials (Study 20062004 and Study 20040215) [see Clinical Trials ( 14.3 )] in which a total of 548 adult or skeletally mature adolescent patients with giant cell tumor of bone received at least 1 dose of Xgeva. Patients received 120 mg Xgeva subcutaneously every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy. Patients receiving concurrent bisphosphonate therapy were excluded from enrollment in both studies. Patients with prior history of ONJ or osteomyelitis of the jaw, an active dental or jaw condition requiring oral surgery, non-healed dental/oral surgery, or any planned invasive dental procedure were excluded from enrollment in Study 20040215. During the trial, serum chemistries including calcium and phosphorus were monitored every 4 weeks. Calcium and vitamin D supplementation was recommended but not required. Of the 548 patients who received Xgeva, 467 patients were treated with Xgeva for ≥ 1 year, 323 patients for ≥ 2 years, and 255 patients for ≥ 3 years. The median number of doses received was 33 (range: 4-138 doses) and the median number of months on-study was 60 (range: 0-140 months). Fifty-seven percent of the enrolled patients were women and 82% were White. The median age was 33 years (range: 13-83 years); a total of 19 patients were skeletally mature adolescents (12 to < 17 years of age). The common adverse reaction profile of Xgeva in patients with giant cell tumor of bone was generally similar to that reported in Studies 20050136, 20050244, and 20050103. The most common adverse reactions in patients (incidence ≥ 10%) were arthralgia, back pain, pain in extremity, fatigue, headache, nausea, nasopharyngitis, musculoskeletal pain, toothache, vomiting, hypophosphatemia, constipation, diarrhea, and cough. The most frequent serious adverse reactions were osteonecrosis of the jaw (3.6%), bone giant cell tumor (1.5%), anemia (1.1%), pneumonia (0.9%), and back pain (0.9%). The most frequent adverse reactions resulting in discontinuation of Xgeva was osteonecrosis of the jaw (incidence of 3.6%). The adverse reaction profile appeared similar in skeletally mature adolescents and adults. Hypocalcemia and Hypophosphatemia Moderate to severe hypocalcemia (corrected serum calcium less than 8 mg/dL or less than 2 mmol/L) occurred in 5% of patients treated with Xgeva. Severe hypophosphatemia (serum phosphorus less than 2 to 1 mg/dL or less than 0.6 to 0.3 mmol/L) occurred in 20% of patients treated with Xgeva. Osteonecrosis of the Jaw (ONJ) In the pooled analysis of Study 20062004 and Study 20040215, ONJ was confirmed in 7% of patients who received Xgeva (median number of doses received: 33; range: 4-138 doses). Study 20140114 (NCT03301857) was a 5-year long term follow-up study for patients (n = 85) who completed Study 20062004. In Study 20062004 and Study 20140114 combined, ONJ was confirmed in 7% of patients who received Xgeva (median time on trial 62.2 months (range 0 - 173). The combined patient-year adjusted incidence (number of events per 100 patient years) of confirmed ONJ was 0.2% during the first year of treatment, 1.5% in the second year, 1.8% in the third year, 2.1% in the fourth year, 1.4% in the fifth year, and 1.5% thereafter [see Warnings and Prec autions ( 5.4 )] . Atypical Subtrochanteric and Diaphyseal Fracture In the pooled analysis of Study 20062004 and Study 20040215, atypical femoral fracture was observed in 0.9% of patients who received Xgeva (median number of doses received: 33; range: 4-138 doses). In Study 20062004 and Study 20140114, the combined incidence of confirmed atypical femoral fracture was 1.3% of patients who received Xgeva [see Warnings and Precautions ( 5.5 )] . Hypercalcemia Following Treatment Discontinuation In the pooled safety population, 0.7% of patients experienced serious adverse events of hypercalcemia > 30 days following treatment discontinuation that was recurrent in some patients [see Warnings and Precautions ( 5.6 )] . Hypercalcemia of Malignancy Xgeva was evaluated in an open-label, single-arm trial (Study 20070315) in which 33 patients with hypercalcemia of malignancy (with or without bone metastases) refractory to treatment with intravenous bisphosphonate therapy were enrolled [see Clinical Trials ( 14.4 )] . The adverse reaction profile of Xgeva in patients with hypercalcemia of malignancy was similar to that reported in Studies 20050136, 20050244, 20050103, 20062004, and 20040215. Adverse reactions occurring in greater than 20% of patients were nausea (30%), dyspnea (27%), decreased appetite (24%), headache (24%), peripheral edema (24%), vomiting (24%), anemia (21%), constipation (21%), and diarrhea (21%). The following adverse reactions of Grade 3 or greater severity related to study therapy were reported on-study: fatigue (3%) and infection (6%). Grade 3 laboratory abnormalities included hypomagnesemia (3%), hypokalemia (3%), and hypophosphatemia (76%) of patients. No deaths on-study were related to Xgeva therapy. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of Xgeva. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Hypocalcemia: Severe symptomatic hypocalcemia, including fatal cases [see Contraindications ( 4.1 ) and Warnings and Precautions ( 5.3 )] . Hypercalcemia: Severe symptomatic hypercalcemia following treatment discontinuation can occur [see Adverse Reactions ( 6 ) and Warnings and Precautions ( 5.6 )] . Hypersensitivity, including anaphylactic reactions [see Contraindications ( 4.2 ) and Warnings and Precautions ( 5.2 )] . Musculoskeletal pain, including severe musculoskeletal pain. Positive re-challenge has been reported. Lichenoid drug eruptions (e.g., lichen planus-like reactions). Alopecia. Injection site reactions including injection site pain.

FDA lists 4 drug label records with DENOSUMAB as the active ingredient. The most common dosage forms and the manufacturers with the most records are summarised below; strengths, pack sizes and inactive ingredients can still differ between apparently similar products.

5 FDA recall record(s) match this product name or manufacturer. A match means the firm or product name appears in the enforcement report; confirm lot numbers and dates against the official FDA notice before acting.

What is XGEVA used for?
1 INDICATIONS AND USAGE Xgeva is a RANK ligand (RANKL) inhibitor indicated for: Prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors. ( 1.1 ) Treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity. ( 1.2 , …

Who makes XGEVA?
Amgen, Inc is the labeler of record for XGEVA. 4 FDA label records share the active ingredient DENOSUMAB, so generic and branded versions may come from different companies; the manufacturer named on your pack is the one that matters for any enquiry.

What form does XGEVA come in?
administered by subcutaneous. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is XGEVA prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Are there other products containing DENOSUMAB?
Yes. 4 FDA drug label records list DENOSUMAB as the active ingredient. Products with the same active ingredient can usually be substituted only when a prescriber or pharmacist confirms it is appropriate.

Has XGEVA been recalled?
5 FDA recall record(s) match this product name or manufacturer. Review the recall and safety notices section on this page and confirm lot numbers against the official FDA enforcement report.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.